This proposal is to continue the follow-up of children and young adults who were successfully treated for Wilms tumor on protocol studies of the National Wilms Tumor Study Group (NWTSG), as well as their offspring. With current therapy, 90 percent of children treated for Wilms tumor will be cured of their disease. However, survivors are at risk for delayed complications of their disease and treatment that can compromise the quality and duration of that survival. Therapy for Wilms tumor has changed over time but still includes surgery, multi-agent chemotherapy, and (for some) radiation therapy. As children are treated for Wilms tumor in early childhood, it has taken many years of follow-up to appreciate some of these long- term effects. For some, we are just beginning to better define these effects 10-20 years post treatment, The mechanisms underlying many of these long term-complications remain unknown, and thus preventive strategies have yet to be established. In addition, as we unravel the complex genetic heterogeneity surrounding the etiology and pathogenesis of Wilms tumor, this may provide important clues to the mechanisms underling long-term complications. With respect to late effects, we will determine the incidence, spectrum and mechanisms of disease, treatment and host-related risk factors for selected life-threatening chronic toxicities in Wilms tumor patients. These include a) congestive heart failure b) respiratory failure c) renal failure and d) second malignant neoplasms (SMN). Related to this, we will determine the incidence and cause of late mortality in Wilms tumor patients and compare with age and sex-specific national population rates. Reproductive epidemiology will be studied with respect to natality, pregnancy outcomes and complications, and congenital or hereditary diseases in the offspring. By using established family history data and pedigrees and following offspring of survivors, heritability and recurrence risks will be estimated and clinical heterogeneity will be explored. We will collaborate with molecular biologists by facilitating access to particularly informative subgroups of Wilms tumor patients.